Thrombocytopenia, Isolated, Stem Cell Transplant Complications
Conditions
Keywords
Azacitidine, N-Acetyl-L-cysteine, Prolonged Isolated Thrombocytopenia, Hematopoietic Stem Cell Transplantation
Brief summary
Prolonged isolated thrombocytopenia (PIT) that is refractory to conventional treatments has remained a critical complication after allogeneic hematopoietic cell transplantation since decades years ago. Recombinant human thrombopoietin (rhTPO) is the main therapy in clinical practice, but remains low efficiency for PIT. Demethylating drugs have shown thier potential in high-risk myelodysplastic syndromes (MDS) and acte myeloid leukemia (AML). In addition, decitabine has demonstrated its efficacy of over 70% for response rate in treatment for PIT in early clinical trials with elusive mechanism. Preliminary experiments revealed that PIT was associated with abnormality of oxidation microenvironment, and N-Acetyl-L-cysteine (NAC) was the most commonly used antioxidant. Therefore, the investigators have been wondering whether Azacitidine in combination with NAC could improve PIT post HSCT and explore the possible mechanism of it.
Detailed description
Prolonged isolated thrombocytopenia (PIT) that is refractory to conventional treatments has remained a critical complication after allogeneic hematopoietic cell transplantation since decades years ago. Recombinant human thrombopoietin (rhTPO) is the main therapy in clinical practice, but remains low efficiency for PIT. Demethylating drugs have shown thier potential in high-risk myelodysplastic syndromes (MDS) and acte myeloid leukemia (AML). In addition, decitabine has demonstrated its efficacy of over 70% for response rate in treatment for PIT in early clinical trials with elusive mechanism. Preliminary experiments revealed that PIT was associated with abnormality of oxidation microenvironment, and N-Acetyl-L-cysteine (NAC) was the most commonly used antioxidant. Furthermore, AZA had shown its potential in immune regulation. Therefore, the investigators have been wondering whether Azacitidine in combination with NAC could improve PIT post HSCT and explore the possible mechanism of it.
Interventions
DRUGAzacitidine
28 days for one cycle, evaluation post 3 cycles of treatment. Continue if response exists, otherwise, quit the trial and seek for other therapies.
28 days for one cycle, evaluation post 3 cycles of treatment. Continue if response exists, otherwise, quit the trial and seek for other therapies.
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Arm1: Control Arm2:AZA+NAC
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Platelet count ≤ 30 × 10\^9/L persistently at day 60 post-HSCT or later; * Neutrophil and hemoglobin were well recovered; * Full donor chimerism was achieved;
Exclusion criteria
* Patients with malignancy relapse; * Active infections; * Grade Ⅲ-Ⅳ acute graft-versus-host disease or severe chronic graft-versus-host disease according to National Institute of Health criteria; * Severe organ damage; * Thrombosis requiring treatment;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| platelet reconstruction | From date of randomization until the date of platelet reconstruction, assessed up to 100 days | platelet count above 50\*10\^9/L independent of transfusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| overall survival | From date of randomization until the date of death from any cause, assessed up to 1 year | the time from the date of day 1 post HSCT to the date of death due to any cause |
| overall response rate | From date of randomization until the date of platelet count between 30*10^9/L and 50*10^9/L, assessed up to 100 days | platelet count evaluating above 30\*10\^9/L but below 50\*10\^9/L independent of platelet transfusion |
Other
| Measure | Time frame | Description |
|---|---|---|
| infection | From date of randomization until the date of diagnose of infection, assessed up to 100 days | clinical diagnose of infection or evidence of next generation of sequencing（NGS）of body fluid or CT or culture of samples collected from patients |
| Severe adverse events | From date of randomization until the date of occurrence of any severe adverse event, assessed up to 100 days | any events that prevent the clinical trial continue besides hepatic injury renal function impairment, et al. |
Countries
China
Contacts
Primary ContactYue Han, PhD,MD
Backup ContactDepei Wu, PhD,MD
Outcome results
None listed